Reactome | DHRSX reduces dolichal to dolichol

DHRSX reduces dolichal to dolichol

Stable Identifier

R-HSA-9937340

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytoplasmic side of endoplasmic reticulum membrane, cytosol, early endosome membrane

Synonyms

a di-trans,poly-cis-dolichal + NADPH + H(+) => a di-trans,poly-cis-dolichol + NADP(+)

ReviewStatus

5/5

Locations in the PathwayBrowser

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Metabolism of proteins (Homo sapiens)

- Post-translational protein modification (Homo sapiens)
  - Asparagine N-linked glycosylation (Homo sapiens)
    - Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein (Homo sapiens)
      - Synthesis of substrates in N-glycan biosythesis (Homo sapiens)
        
        Synthesis of dolichyl-phosphate (Homo sapiens)
        
        DHRSX reduces dolichal to dolichol (Homo sapiens)

General

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DHRSX (Polyprenol dehydrogenase) catalyzes the reduction of dolichal (DCHAL) to dolichol (DCHOL) coupled to the oxidation of NADPH + H+ to NADP+. Oxidoreductase reactions are reversible, and their direction is largely determined by the ratio of the reduced to the oxidized cofactor. In cells, the ratio of NAD+ to NADH is >100:1, while the ratio of NADP+ to NADPH is <1:10. DHRSX uses NAD and NADP with comparable efficiencies, so it is plausible that high cellular concentrations of NAD+ can drive DHRSX-catalyzed oxidation of polyprenol to polyprenal and high concentrations of NADPH can simultaneously drive DHRSX-catalyzed reductions of polyprenal and dolichal (Wilson et al. 2024).

The majority of DHRSX in cells expressing a FLAG-tagged construct is associated with lipid droplets and only a minor fraction is associated with the ER membrane (Wilson et al. 2024). Given the hydrophobic nature of the ER-associated substrate, however, the ER-localized form of the enzyme is annotated as the catalyst of this reaction.

Literature References

PubMed ID	Title	Journal	Year
38821050	A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis Wilson, MP, Kentache, T, Althoff, CR, Schulz, C, de Bettignies, G, Mateu Cabrera, G, Cimbalistiene, L, Burnyte, B, Yoon, G, Costain, G, Vuillaumier-Barrot, S, Cheillan, D, Rymen, D, Rychtarova, L, Hansikova, H, Bury, M, Dewulf, JP, Caligiore, F, Jaeken, J, Cantagrel, V, Van Schaftingen, E, Matthijs, G, Foulquier, F, Bommer, GT	Cell	2024